Immunotherapy may be efficacious in patients with HIV-associated Kaposi's sarcoma

Among a small cohort of patients with HIV-associated Kaposi's sarcoma treated with immune checkpoint inhibitors, more than 65 percent had partial or complete remission.

The study is published in Cancer Immunology Research, a journal of the American Association for Cancer Research, by Natalie Galanina, MD, oncologist at Moores Cancer Center at UC San Diego Health.

"Despite the successful and prevalent use of antiretroviral medications to treat human immunodeficiency virus (HIV)-positive patients, about 15 percent of this population still develops Kaposi's sarcoma, which is an incurable malignancy with significant morbidity," said Galanina. "Due to a paucity of novel therapeutic options for this disease in recent decades, we wanted to investigate if immune checkpoint inhibition was effective in treating this virally mediated cancer."

The standard of care for patients with Kaposi's sarcoma is liposomal doxorubicin, a type of chemotherapy. While roughly half of patients respond to this therapy, most suffer relapses and require repeated treatments, noted Galanina. Because the standard of care is not curative, and Kaposi's sarcoma can persist in patients with an undetectable viral load, new treatments for this disease represent a clinically unmet need, she explained.

Galanina and colleagues analyzed data from nine men with Kaposi's sarcoma treated with anti-PD-1 immune checkpoint inhibitors at Moores Cancer Center between August 2013 and December 2017. All patients had received retroviral therapy and a median of one prior line of treatment for Kaposi's sarcoma. Eight patients were treated with nivolumab (Opdivo), while one patient was treated with pembrolizumab (Keytruda).

Following treatment with immune checkpoint inhibition, five patients had a partial response, three patients had stable disease, and one patient had complete remission. All patients remained on treatment, and no patient had shown disease progression at 6.5 months of follow-up.

PD-L1 expression was negative in all four evaluable patients. Furthermore, all three evaluable patients had low TMB (between 1-4 mutations per megabase).

"Typically, checkpoint blockade immunotherapy is more effective in patients with high TMB and/or high expression of PD-L1, yet we saw many patients who responded to treatment without these characteristics," said Galanina. "It is possible that the viral immunogenomic mutanome is sufficient to induce changes to the immune system, enabling a response to treatment with checkpoint inhibition."

While treatment with standard chemotherapy can have significant side effects, patients treated with PD-1 inhibitors experienced limited toxicity in this study, noted Galanina. "Importantly, treatment with PD-1 inhibitors did not cause myelosuppression, which is an important finding in this patient population," she added.

Furthermore, seven patients treated with PD-1 inhibitors had an increase in both CD4+ and CD8+ T cell levels, although not statistically significant.

"Based on these results, we think that PD-1 checkpoint blockade may present a promising, novel therapeutic option for HIV-associated Kaposi's sarcoma with high efficacy and low toxicity," said Galanina.

Limitations of the study include a small sample size and the paucity of available archival tissue material to corroborate PD-L1 expression findings.

I had Kaposi’s sarcoma in 2001 when I was ART naive. I have lost track of what I was treated with but also started ART at that time and have been HIV undetectable since and KS in remission (if that is proper way to describe. After reading this article I am wondering if I am in the majority of PWA who had KS so many years ago.

I had Kaposi’s sarcoma in 2001 when I was ART naive. I have lost track of what I was treated with but also started ART at that time and have been HIV undetectable since and KS in remission (if that is proper way to describe. After reading this article I am wondering if I am in the majority of PWA who had KS so many years ago.

I was diagnosed with full blown AIDS in 1993 and also had KS at that time among other OI's. Like many others I was told I had one to three years to live. I refused treatment for KS as it didn't work anyway but made people very sick and they usually died within a year with treatment based on my own limited personal observation. In the words of the oncologist, "the treatment would leave me flat on my back for a year with projectile vomiting." The treatment was aggressive radiation followed by aggressive general injection chemo therapy (not lesion specific). After treatment, I was told there would be a 95% confidence interval that the KS would return in one to three months. I don't personally know of any case during that time period that anyone survived treatment for more than a year. So for me it was a quality, not quantity of life issue. Strangely, for reasons not known except that I was found to have an extraordinarily high NK cell count, the KS went partially into remission in 1995 and fully into remission after starting three drug therapy in 1996. It reappeared about five years ago as a single lesion (biopsy proven) and has remained stable ever since. I still have it and I have refused treatment for it as I don't think anything really gets "rid" of it. HART is the best treatment against it that I know of. My viral load remains undetectable since starting HART. It does come back for some but not others even when continuously on HART and undetectable viral load. But if it returns on HART, it doesn't seem to progress in the aggressive manner that it did before the days of HART. But even after having been completely clear of it for 17 years it did return so I don't know if anyone is ever completely clear of it.

I was diagnosed with full blown AIDS in 1993 and also had KS at that time among other OI's. Like many others I was told I had one to three years to live. I refused treatment for KS as it didn't work anyway but made people very sick and they usually died within a year with treatment based on my own limited personal observation. In the words of the oncologist, "the treatment would leave me flat on my back for a year with projectile vomiting." The treatment was aggressive radiation followed by aggressive general injection chemo therapy (not lesion specific). After treatment, I was told there would be a 95% confidence interval that the KS would return in one to three months. I don't personally know of any case during that time period that anyone survived treatment for more than a year. So for me it was a quality, not quantity of life issue. Strangely, for reasons not known except that I was found to have an extraordinarily high NK cell count, the KS went partially into remission in 1995 and fully into remission after starting three drug therapy in 1996. It reappeared about five years ago as a single lesion (biopsy proven) and has remained stable ever since. I still have it and I have refused treatment for it as I don't think anything really gets "rid" of it. HART is the best treatment against it that I know of. My viral load remains undetectable since starting HART. It does come back for some but not others even when continuously on HART and undetectable viral load. But if it returns on HART, it doesn't seem to progress in the aggressive manner that it did before the days of HART. But even after having been completely clear of it for 17 years it did return so I don't know if anyone is ever completely clear of it.

sorta proves what i've been sayin for decades. Everyone is different genetically, and everyone reacts differently to every drug, side effects especially...Steven, glad you made it thru. I went undetectable from '97, having started AZT in early 90. Thank god Conant put me on a low dose (forget exact). Kaiser killed a buddy of mine with 5 pills 5x a day about that time... -- Edward KDumaguete, Negros OrientalPhilippines

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